INTERSTITIAL PNEUMONIAS

INTERSTITIAL PNEUMONIAS

Dr. Branimir PenevDr. Branimir PenevClinic of Diagnostic ImagingTokuda Hospital Sofia

Definition

� The interstitial pneumonias are a heterogeneous group of nonneoplastic, diffuse lung diseases associated with varying degrees of interstitial lung inflammation and fibrosis

� Idiopathic interstitial pneumonias (IIPs) occur � Idiopathic interstitial pneumonias (IIPs) occur without known cause

� Identical histologic patterns, radiographic appearances and clinical symptoms may occur in association with collagen-vascular disease, drug reactions, smoking and infection

The interstitium

The interstitium includes the space between the epithelial and endothelial basement membranes and is the primary site of disease in the idiopathic interstitial pneumonias. idiopathic interstitial pneumonias.

These disorders also frequently affect the air spaces, peripheral airways, and vessels, as well as their respective epithelial and endothelial linings

Classification� One of the earliest histopathological

classifications of ILD was proposed by Liebow and Carrington in 1969

� The ATS–ERS classification of idiopathic

interstitial pneumonias (IIPs),2002, defines the morphologic patterns on which clinical-the morphologic patterns on which clinical-radiologic-pathologic diagnosis of IIPs is based. ATS-ERS classification is the result of a multidisciplinary consensus

� IIPs include seven entities:

UIP , NSIP , COP , RB-ILD , DIP , LIP , AIP

ATS/ERS classification algorithm for ILDs

Classification

� The classification of IIPs is based on histologic criteria, but each histologic pattern is associated with a characteristic CT pattern

� In their idiopathic form, IIPs are rare diseases. More frequent disorders such as sarcoidosis, More frequent disorders such as sarcoidosis, vasculitis, and connective tissue diseases can display identical morphologic patterns

� IIPs are considered “prototypes” for these

morphologic alterations

Multidisciplinary approach

� The American Thoracic Society and European Respiratory Society recommendations of 2002 provide a framework for the diagnosis of interstitial lung disease (ILD) and proposed an integrated clinical, radiological and histopathological approach.

� These recommendations represent a break with tradition � These recommendations represent a break with tradition by replacing the ‘gold standard’ of histopathology with the combined ‘silver standards’ of clinical, imaging and istopathological information.

� Incidence of ILD- approximately 50 cases per 100,000 per year

Clinical Features of Patients with IIPs according to the ATS-ERS Consensus Statement

MorphologicPattern

HistopathologicFeatures

Distribution at CT High-Resolution CT Features

UIP Spatial and temporal heterogeneity,architectural distortion, fibroblastic foci

Apicobasal gradient,subpleural

Macrocystichoneycombing, reticular opacities, traction bronchiectasis,architectural distortion,focal ground-glass opacity

NSIP Spatial and temporal homogeneity;cellular pattern shows mild to moderate

No obvious gradient,subpleural, symmetric

Ground-glass opacities, irregular linear or reticular opacities, micronodules,mild to moderate

interstitial chronic inflammation;fibrosing pattern shows dense or loose interstitialfibrosis

symmetric micronodules,consolidation, microcystichoneycombing

COP Patchy distribution of intraluminal organizing fibrosis in distal airspaces,preservation of lung architecture, uniform temporal appearance

Patchy, peripheral or peribronchial, basal predominance,sometimes sparingof subpleural space, migration tendency

Airspace consolidation, mild bronchialdilatation, ground-glassopacities, large nodules (rare)

MorphologicPattern

Histopathologic Features Distribution at CT

High-Resolution CT Features

AIP Diffuse alveolar damage; exudativephase shows hyaline membranes,diffuse alveolar infiltration by lymphocytes; organizing phase shows alveolar wall thickening due to fibrosis, pneumocytehyperplasia

Lower lung predominancesymmetric,bilateral

Exudative phase shows groundglass opacities, airspace consolidation;organizing phase showsbronchial dilatation, architectural distortion

RB-ILD Bronchiolocentric accumulation ofalveolar macrophages containingbrown particles, mild bronchiolar

Diffuse or upper lungpredominance

Centrilobular nodules, patchy ground-glass opacities, bronchialbrown particles, mild bronchiolar

fibrosispredominance opacities, bronchial

wall thickening

DIP Diffuse accumulation of macrophages in distal airspaces, mild interstitial fibrosis, mild chronic inflammation

Apicobasalgradient,peripheral predominance

Ground-glass opacities, irregular linear or reticular opacities,sometimes cysts

LIP Diffuse infiltration of alveolarsepta by lymphoid cells, l ymphoidhyperplasia frequent

Basilar predominanceor diffuse

Ground-glass opacities, perivascular cysts, septal t hickening, centrilobular nodules

IPF/UIP- distribution and CT appearancesHistopathologic Features Distribution

at CTHigh-Resolution CT

Features

Spatial and temporal heterogeneity,architectural distortion, fibroblastic foci .cystically dilated air spaces honeycomb pattern , dense fibrosis , beneath the pleura

Apicobasalgradient,subpleural

Macrocystic honeycombing, reticular opacities, traction bronchiectasis, architectural distortion, focal ground-glass opacity

IPF-DiagnosisIn patients who show the characteristic distribution and high-resolution CT pattern of UIP and the appropriate clinical features, the diagnosis can be reliably made without biopsy

ATS-ERS Criteria for Diagnosis of IPF in the Absence of Surgical Lung Biopsy

Major criteria

• Exclusion of other known causes of interstitial lung disease (eg, toxic effects of certain drugs, environmental exposures, and connective tissue diseases)

• Abnormal results of pulmonary function studies, including evidence of restriction and impaired gas exchange

• Bibasilar reticular abnormalities with minimal ground-glass opacities at HRCT• Bibasilar reticular abnormalities with minimal ground-glass opacities at HRCT• Transbronchial lung biopsy or bronchoalveolar lavage shows no features to

support an alternative diagnosis

Minor criteria• Age 50 y• Insidious onset of otherwise unexplained dyspnea on exertion• Duration of illness 3 mo• Bibasilar inspiratory crackles (dry or “Velcro” type)

Histologic confirmation should be obtained in all patients with atypical imagingfindings, such as extensive ground-glass opacities, nodules, consolidation, or a predominantly peribronchovascular distribution

NSIP- distribution and CT appearancesHistopathologic Features Distribution

at CTHigh-Resolution CT

Features

Spatial and temporal homogeneity;cellular pattern shows mild to moderate interstitial chronic inflammation;fibrosing pattern shows dense or loose interstitial fibrosis

No obvious gradient,subpleural, symmetric

Ground-glass opacities, irregular linear or reticular opacities, micronodules,consolidation, microcystichoneycombing

NSIP

� The mean age range of onset is 40–50 years.

� Worsening dyspnea over several months, cough, fatigue and weight loss.

� Homogeneity is a key feature in differentiating the NSIP pattern from the UIP patternNSIP pattern from the UIP pattern

� NSIP is associated with a variety of imaging and histologic findings, and the diagnostic

approach is highly challenging

� Better response to corticosteroids and favorable prognosis than that of idiopathic pulmonary fibrosis

Comparison of high-resolution CT features between UIP and NSIP

obvious apico-basal gradient no obvious gradient

heterogeneoushomogeneous

honeycombingground-glass opacities

traction bronchiectasismicronodules

UIP NSIP

OP/ COP- distribution and CT appearancesHistopathologic Features Distribution at CT HRCT Features

The histologic hallmark of organizing pneumonia is the presence of granulation tissue polyps in the alveolar ducts and alveoli. Patchy distribution of intraluminal organizing fibrosis in distal airspaces, preservation of lung architecture, uniform temporal appearance.early phase- Ly and plasma cells are seen within a

fibrous tuft

late phase-

Patchy, peripheral or peribronchial, basal predominance, sometimes sparing of subpleural space, migration tendency

Airspace consolidation, mild bronchial dilatation, ground-glass opacities, large nodules (rare)

late phase-fibrosis in respiratory bronchioles and alveolar ducts and interstitial fibrosis

OP/ COP� The consolidations in COP do not represent

an active pneumonia but result from intraalveolarfibroblast proliferations, which may be associated with prior respiratory infection.

� Mean age 55 years old

� Cough and dyspnea, weight loss, sweats, chills, � Cough and dyspnea, weight loss, sweats, chills, intermittent fever, and myalgia

� Most patients recover completely after oral

administration of corticosteroids. Relapse can occur.

� Atypical appearance of COP

RB- ILD - distribution and CT appearancesHistopathologic Features Distribution at CT HRCT Features

Bronchiolocentric accumulation ofalveolar macrophages containingbrown particles, mild bronchiolar fibrosis. Macrophages have dusty brown cytoplasm from the “tobacco pigment”

upper lungpredominance

Centrilobularground-glass nodules, thickening of central and peripheral airways with associated centrilobularemphysema and air trapping

Respiratory Bronchiolitis–associated Interstitial Lung Disease

� RB -ILD is the clinical manifestation of an interstitial lung disease associated with the pathologic lesion of respiratory bronchiolitis, which is found in cigarette smokers.

� When RB is symptomatic, the patient has abnormal results from pulmonary function tests and imaging studies.

The disease usually affects current smokers 30–40 years old� The disease usually affects current smokers 30–40 years old

with more than 30 pack-years of cigarette smoking

� Male-female ratio 2:1.

� Mild symptoms of dyspnea and cough.

� Smoking cessation is the most important component in the therapeutic management of RB-ILD.

DIP- distribution and CT appearancesHistopathologic Features Distribution at CT HRCT Features

Diffuse accumulation of macrophages in distal airspaces, mild interstitial fibrosis, mild chronic inflammation

Apicobasal gradient,peripheral predominance

Ground-glass opacities which correlate histologically with the spatially homogeneous intraalveolaraccumulation of macrophages, irregular linear or reticular opacities-septal thickening ,sometimes cysts

RB-ILD and DIP, imaging findings may overlap and may be indistinguishable from each other

Desquamative Interstitial Pneumonia� DIP is strongly associated with cigarette smoking and is

considered to represent the end of a spectrum of RB-ILD

� DIP also occurs in nonsmokers and has been related to a variety of conditions, including lung infections and exposure to organic dust

� Age - between 30 and 40 years

� Male-to- female ratio 2:1

� Onset of dyspnea and dry cough can progress to respiratory failure

� With smoking cessation and corticosteroid therapy, the prognosis is good

� Progressive disease with eventual death can occur, notably in patients with continued cigarette smoking

LIP- distribution and CT appearancesHistopathologic Features Distribution

at CTHRCT Features

Diffuse infiltration of alveolar septa by lymphoid cells, lymphoid hyperplasia frequentSecondary involved airspaces -proteinaceous fluid and macrophage collections

Basilar predominanceor diffuse,bilateral

Ground-glass opacities, perivascular thin-walled cysts, septal thickening, centrilobular nodules(Ly)The cysts of LIP are usually within the lung parenchyma throughout the mid lung zones - result from air trapping due to peribronchiolar cellular infiltration

Combination of groundglass opacities and thin-walled ,

perivascular cyst in the mid lung zones are highly suggestive of LIP.

Lymphoid Interstitial Pneumonia� As an idiopathic disease, LIP is exceedingly

� It is more common as a secondary disease in association with systemic disorders - Sjőgren syndrome, HIV infection

� More common in women

� Age - between 40 and 50 years� Age - between 40 and 50 years

� Slowly progressive dyspnea and cough over a period of 3 or more years. Fever, night sweats and weight loss.

� In the past, LIP was considered a pulmonary lymphoproliferative disorder

� Corticosteroids are used in the therapy , but response is unpredictable

AIP- distribution and CT appearancesHistopathologic Features Distribution at

CTHRCT Features

Diffuse alveolar damage: exudativephase shows hyaline membranes,diffuse alveolar infiltration by lymphocytes; organizing phase shows alveolar wall thickening due to fibrosis, pneumocyte hyperplasia

Lower lung predominancesymmetric,bilateral

Exudative phase shows groundglass opacities, airspace consolidation;Organizing phase showsbronchial dilatation, architectural distortion

Exudative

phase

Organizing

phase

Chest radiography in AIP reveals bilateral air-space opacification with sparing of the costophrenic angles

Acute Interstitial Pneumonia� AIP is the only entity among the IIPs with acute onset of

symptoms. AIP is a rapidly progressive, organizing form of diffuse alveolar damage. Also known as Hamman-Rich disease

� The patient’s condition usually progresses to respiratory failure that requires mechanical ventilation and corticosteroid therapy, with the development of ARDS

� Death occurs in just over 50 % of cases.

� Wide age range, with a mean of 50 years old

� Typically, a history of viral-like illness exists.

� Men and women are equally affected

� Cigarette smoking does not increase the risk

� Most patients who survive the acute phase of the disease

later progress to lung fibrosis

Prognostic value between UIP and Non-UIP ILD

A confident diagnosis of IPF on HRCT is accurate in 90% of cases. The primary role of HRCT is to separate patients with typical findings of UIP/IPF from those who present with atypical features and who warrant surgical lung biopsy

Flaherty et al; Radiological vs histological diagnosis in UIP and NSIP: survival implications; Thorax 2003;58:143-148